MAPPING NEURAL CIRCUITRY WITH TRANSSYNAPTIC VIRUS

用跨突触病毒绘制神经回路

• 批准号: 8889264
• 负责人: YUCHIN Albert Pan
• 金额: $ 37.24万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8889264
• 关键词: Accounting; Address; Affect; Anatomy; Animal Behavior; Architecture; Autistic Disorder; Behavior; Blindness; Brain; Brain Mapping; Brain imaging; Brain region; Calcium; Cells; Characteristics; Collection; Communities; Complex; Data; Detection; Development; Disease model; Embryo; Environment; Functional Imaging; Genetic; Goals; Health; Human; Image; Infection; Injury; Kinetics; Knowledge; Label; Larva; Lead; Maps; Mediating; Membrane; Methods; Movement; Natural regeneration; Nervous system structure; Neurons; Neurosciences; Optics; Organ; Organism; Parkinson Disease; Pattern; Perception; Physiological; Physiology; Population; Process; Psyche structure; Reagent; Reporter; Resolution; Resources; Retinal Ganglion Cells; Speed; Spinal cord injury; Structure; Synapses; System; Techniques; Technology; Testing; Tetanus Helper Peptide; Tissues; Transgenic Organisms; Vesicular stomatitis Indiana virus; Viral; Virus; Virus Diseases; Vision; Visual; Visual Motion; Zebrafish; base; behavioral study; cell type; functional loss; human disease; imaging modality; in vivo; insight; nervous system disorder; neural circuit; neurodevelopment; novel; novel strategies; prevent; receptor; relating to nervous system; response; tool; transmission process; vector

DESCRIPTION (provided by applicant): Neurons form precise and complex neural circuits to generate perception and behavior. A major goal of neuroscience is to map the large ensemble of neural circuits in the brain and understand how they account for normal brain functions and neurological disorders. The small size and optical transparency of larval zebrafish make it an ideal system to investigate neural circuits in an intact vertebrate organism. However, current techniques for mapping neural circuitry in zebrafish are limited in speed and scale, preventing the full realization of zebrafish's potential for neural circuit studies. To address this gap in technology, we propose to develop a virus-based toolkit that would enable rapid and systematic neural circuit mapping in zebrafish. In preliminary studies, we established that vesicular stomatitis virus (VSV) can be used as a tool to map neural circuits. It efficiently infects zebrafih neurons, spreads rapidly across synapses, and expresses fluorescent reporters for circuit mapping. VSV labeling could also be combined with other imaging methods to probe neuronal function. To extend these studies, we propose three specific aims: Aim 1. We will establish virus-based tools to map neural circuits on a whole-brain scale, in vivo. We will investigate the characteristics of VSV and distribute reagents and neural circuit mapping results to the community. Aim 2. We will develop tools to elucidate connectivity patterns of specific neuronal types. These tools will be able to (1) target initial infection to defined cell types and (2) identfy neurons that are directly connected to them. Aim 3. We will create tools that combine neural circuit mapping with functional analyses. These tools will help bridge the gap between neural circuit structure and function. In summary, this proposal addresses a critical need for zebrafish neural circuit tracing tools and provides a novel approach to combine anatomical and functional analyses. We will utilize these tools to map the circuitry underlying visual function, both as a tet platform and as a resource for studying vision. These tools could be applied throughout the nervous system and facilitate neural circuit studies in the wider community, e.g. neural development, physiology, behavior, regeneration, as well as disease models.

描述（由申请人提供）：神经元形成精确而复杂的神经回路，产生感知和行为。神经科学的一个主要目标是绘制大脑中神经回路的大集合，并了解它们如何解释正常的大脑功能和神经系统疾病。斑马鱼幼体体积小，光学透明，是研究完整脊椎动物神经回路的理想系统。然而，目前用于绘制斑马鱼神经回路的技术在速度和规模上都受到限制，阻碍了斑马鱼神经回路研究潜力的充分实现。为了解决这一技术上的差距，我们建议开发一个基于病毒的工具包，使斑马鱼能够快速和系统地绘制神经回路。在初步研究中，我们确定水疱性口炎病毒（VSV）可以作为绘制神经回路的工具。它能有效地感染斑马鱼神经元，在突触间迅速传播，并表达荧光报告以进行电路制图。VSV标记也可以与其他成像方法结合来探测神经元功能。为了扩展这些研究，我们提出了三个具体目标：目标1。我们将建立基于病毒的工具，在全脑范围内绘制神经回路。我们将调查VSV的特点，并向社区分发试剂和神经回路测绘结果。目标2。我们将开发工具来阐明特定神经元类型的连接模式。这些工具将能够(1)针对确定的细胞类型进行初始感染，(2)识别与它们直接相连的神经元。目标3。我们将创建结合神经回路映射和功能分析的工具。这些工具将有助于弥合神经回路结构和功能之间的差距。总之，该建议解决了对斑马鱼神经回路追踪工具的关键需求，并提供了一种结合解剖和功能分析的新方法。我们将利用这些工具来绘制视觉功能背后的电路，作为视觉研究的平台和资源。这些工具可以应用于整个神经系统，并促进更广泛的神经回路研究，例如神经发育、生理学、行为、再生以及疾病模型。